Complement receptor 4 (CR4 (CD11c/CD18))

Complement receptor 4 (CR4, also known as CD11c/CD18 or αXβ2 integrin) is a heterodimeric transmembrane glycoprotein composed of an alpha subunit (CD11c, encoded by ITGAX) and a beta subunit (CD18, shared with other β2 integrins). It is primarily expressed on myeloid lineage leukocytes—such as monocytes, macrophages, neutrophils—as well as dendritic cells, natural killer cells, activated T lymphocytes, B lymphocytes (especially memory B cells), microglia, Kupffer cells, cytotoxic T cells, platelets. CR4 functions mainly as an adhesion receptor involved in immune responses. It binds to complement fragment iC3b deposited on opsonized pathogens or apoptotic bodies and also interacts with extracellular matrix proteins like fibrinogen and ICAM‑1. This enables it to mediate key processes such as phagocytosis of opsonized particles/cells, cellular adherence to tissues during inflammation or infection, migration of leukocytes through tissues, activation/proliferation/differentiation of memory B lymphocytes within germinal centers, and podosome formation for motility. While structurally similar to complement receptor 3 (CR3), CR4 has distinct intracellular signaling properties that result in some functional specialization—most notably dominating monocyte/macrophage/dendritic cell adhesion to fibrinogen while CR3 dominates phagocytosis of iC3b-opsonized targets. Both receptors participate equally in podosome formation related to cellular motility but differ subtly in ligand specificity due to differences at their metal-ion dependent adhesion site (MIDAS). CR4 serves as a widely used marker for murine dendritic cells due to high expression levels. Its dysregulation has been implicated in inflammatory diseases and certain cancers—notably those involving aberrant B-cell populations expressing CD11c/CR4. No approved drugs specifically target CR4 directly; however, its centrality makes it a potential therapeutic target under investigation for modulating immune responses. In summary, Complement receptor 4 is a β2-integrin family member critical for innate immunity through roles in phagocytosis/adherence/migration across multiple leukocyte types. It acts via recognition of complement fragments like iC3b on pathogens/apoptotic bodies or matrix proteins such as fibrinogen during inflammation/infection.

Other names

CD11c/CD18αXβ2 integrinITGAX/ITGB2 heterodimerp150,95